It has long been known to form peptides by the step-by-step combining of amino acids in solution. However, the solid-phase peptide synthesis described in 1962 by Merrifield (Fed. Proc., Fed. Amer. Soc. Exp. Biol. 21 [1962] 412) has proven to be substantially more successful; in this method, the condensation of the individual amino acids is performed on a solid support material (preferably slightly cross-linked polystyrene), until finally the finished polypeptide is split off from the support. The advantage of the Merrifield synthesis is that it is performed in heterogeneous phase, so that it becomes easily possible to separate the reagents used in the peptide synthesis from the actual synthesis product bound to the support material. The disadvantage of the Merrifield synthesis is that the chemical reactions used for the sequential synthesis are not, of course, quantitative, so that to some extent the reaction does not take place as desired, and therefore contaminating peptides are simultaneously synthesized and can be separated only with extraordinary difficulty. Particularly in the case of the longer amino acid sequences of 50 and more amino acids, even if the individual steps are 99% effective, the multiplicity of the reactions results in an immense number of by-products in addition to the targeted peptide, which may have either excessively short amino acid chains or may have defects in the amino acid sequence.
Therefore, there has been a need for improving the fundamentally simple Merrifield synthesis so as to make it possible to form peptides of even higher molecular weight having a great number of amino acids in the chain, and containing little or no undesired by-products.